Essential role of PR-domain protein MDS1-EVI1 in MLL-AF9 leukemia.
Blood
; 122(16): 2888-92, 2013 Oct 17.
Article
em En
| MEDLINE
| ID: mdl-24021671
ABSTRACT
A subgroup of leukemogenic mixed-lineage leukemia (MLL) fusion proteins (MFPs) including MLL-AF9 activates the Mecom locus and exhibits extremely poor clinical prognosis. Mecom encodes EVI1 and MDS1-EVI1 (ME) proteins via alternative transcription start sites; these differ by the presence of a PRDI-BF1-RIZ1 (PR) domain with histone methyltransferase activity in the ME isoform. Using an ME-deficient mouse, we show that ME is required for MLL-AF9-induced transformation both in vitro and in vivo. And, although Nup98-HOXA9, MEIS1-HOXA9, and E2A-Hlf could transform ME-deficient cells, both MLL-AF9 and MLL-ENL were ineffective, indicating that the ME requirement is specific to MLL fusion leukemia. Further, we show that the PR domain is essential for MFP-induced transformation. These studies clearly indicate an essential role of PR-domain protein ME in MFP leukemia, suggesting that ME may be a novel target for therapeutic intervention for this group of leukemias.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Leucemia Aguda Bifenotípica
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Regulação Leucêmica da Expressão Gênica
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Proteínas de Fusão Oncogênica
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Proteína de Leucina Linfoide-Mieloide
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article